Although sleep disruption and irregularities, including insomnia, are a widespread and pervasive problem, there are few systems for the treatment and/or enhancement of sleep. For example, previously described devices and techniques for the treatment of sleep disorders have included the use of cooling therapies, including cooling applied to a patient's forehead, to enhance sleep. This has been described, for example, in U.S. Pat. Nos. 8,425,583, and 8,236,038, each of which are herein incorporated by reference in their entirety. Thus, there is evidence for the enhancing sleep by cooling a subject's skin (e.g., forehead), perhaps by taking advantage of a mechanism involving cooling of underlying brain regions. This clinically demonstrated effect may suggest that warming (relative to ambient temperature), rather than cooling, the subject's forehead would have a generally deleterious effect on sleep. However, to date, research touching on the effects of applying higher temperatures to a subject's skin, and specifically a subject's forehead, is somewhat inconclusive.
In general, preclinical studies have suggested that the control of sleep and thermoregulation are integrated at the level of the hypothalamus. Human studies have shown that manipulation of environmental temperature by various means can impact on sleep, however it is not well understood how selective regions of the body can influence hypothalamic sleep and thermoregulatory centers. Clinical insomnia and sleeplessness in general are characterized by transient or chronic difficulty initiating and maintaining sleep though it has been unclear if alterations in thermoregulation play a significant role in the pathophysiology or treatment of the disorder. Physiological and neuroanatomical studies show that the forehead is a region of the body that has unique properties suggesting it may play a prominent role in impacting the hypothalamic control of thermoregulation and by extension may influence the hypothalamic thermoregulatory control of sleep.
Insomnia is most often described as the inability to fall asleep easily, to stay asleep or to have quality sleep in an individual with adequate sleep opportunity. In the U.S., population-based estimates of either chronic or transient insomnia range from 10 to 40% of the population, or 30 to 120 million adults in the United States. Similar prevalence estimates have been reported in Europe and Asia. Across studies, there are two age peaks: 45-64 years of age and 85 years and older. Women are 1.3 to 2 times more likely to report trouble sleeping than men, as are those who are divorced or widowed, and have less education. In the U.S., the economic burden of insomnia approaches $100 billion, in direct health care costs, functional impairment, increased risk of mental health problems, lost productivity, worker absenteeism and excess health care utilization. It is recognized as a public health problem, contributing to more than twice the number of medical errors attributed to health care workers without insomnia episodes. Currently available treatments for insomnia, however, are not entirely satisfactory for a variety of reasons. Sedative-hypnotics are not a complete solution to the problem of insomnia as they are associated with significant adverse events such as the potential for addiction/dependence, memory loss, confusional arousals, sleep walking and problems with coordination that can lead to falls and hip fractures. The majority of insomnia patients would prefer a non-pharmaceutical approach to their insomnia complaints. Cognitive behavior therapy, while effective, is an expensive and labor intensive treatment that is not widely available and is not always covered by health insurance. Over the counter approaches to the treatment of insomnia including a variety of medications and devices suffer from inadequate clinical studies demonstrating significant effects in insomnia patients, as well as potentially dangerous side effects. A large need exists, therefore, for a safe, effective, non-invasive, non-pharmaceutical device for the treatment of sleep including treatment of sleep disorders.
Recent advances have been made in the neurobiology of sleep and in the neurobiology of insomnia that can inform innovative treatments for insomnia. “Hyperarousal”, on a variety of physiological levels, represents the current leading pathophysiological model of insomnia. The degree to which this hyperarousal is mediated by alterations in thermoregulatory control is unclear. Insomnia patients have been shown to have increased whole brain metabolism across waking and sleep in relation to healthy subjects; resting metabolic rate, heart rate and sympathovagal tone in HRV, cortisol secretion in the evening and early sleep hours, beta EEG activity during NREM sleep, increased levels of cortical glucose metabolism, especially in the frontal cortex, associated with higher levels of wakefulness after sleep onset, impairments in the normal drop in core body temperature around the sleep onset period; and cognitive hyperarousal resting on the pre-sleep thoughts of insomnia patients, often described as “racing,” unstoppable, and sleep-focused. Insomnia patients have demonstrated increases in beta EEG spectral power that correlate with increased metabolism in the ventromedial prefrontal cortex during NREM sleep. Improvements in sleep in insomnia patients have been associated with improvements in prefrontal cortex function as measured by functional neuroimaging.
Considerable evidence suggests that sleep and thermoregulation are integrated at the level of the hypothalamus. Development of interventions designed to impact on these relationships may be fruitful in the design of interventions for the treatment of insomnia.
The induction, maintenance and timing of wake, non-rapid eye movement sleep (NREM) or slow wave sleep (SWS), and rapid eye movement (REM) sleep are the products of complex interactions among multiple structures and mechanisms which are widely distributed throughout the brain. Reciprocal interactions between sleep and wake promoting systems ensure that the behavioral state of sleep-wakefulness is altered as per requirement. Prominent among these sleep-promoting structures are the pontine tegmentum and adjacent neuronal groups involved in the generation of REM sleep features. On the other hand the NREM sleep is promoted by several areas including the medial preoptic area (mPOA), the lateral preoptic area (lPOA), the ventrolateral preoptic area (vlPOA), the median preoptic nucleus (mnPO), and the medial septum, which are referred to as basal forebrain (BF) areas (Sherin et al., 1996; John and Kumar, 1998; Gong et al., 2000; Lu et al., 2000; Srividya et al., 2004, 2006). There are external and internal factors that influence the swing of sleep-wakefulness toward either sleep or awake state. The BF plays a strategic role in integrating thermoregulation and sleep regulation.
Body temperature regulation is a fundamental homeostatic function that is regulated by the central nervous system. The preoptic area (POA, such as the mPOA, mnPOA, lPOA, vlPOA) is considered the most important thermoregulatory site in the brain on the basis of thermoregulatory responses elicited by local warming and cooling, lesion, stimulation and single neuronal recording, and many other techniques (Nakayama et al., 1961, 1963; Boulant and Hardy, 1974; Boulant, 1981; Boulant and Dean, 1986). The thermosensitive neurons in the POA receive and integrate cutaneous and deep body thermal information. These neurons are tonically active at thermoneutral temperature, and control the thermoregulatory efferent pathway (Nakayama et al., 1961, 1963).
The existence of sleep-wake promoting areas in the brain was first indicated by von Economo. Postmortem examination of the brains of Encephalitis lethargica patients with hypersomnolence showed that they had lesions at the junction of the midbrain and the diencephalon (von Economo, 1930). On the other hand, some patients with lesion in the anterior hypothalamic-POA (POAH) had insomnia. The concept of the POA as a sleep-promoting area and the posterior hypothalamus as the wake promoting area was supported by several lines of animal experiments employing stimulation, lesion, single unit recording, neural transplantation, functional magnetic resonance imaging (fMRI), and c-fos studies (Nauta, 1946; Sterman and Clemente, 1962; McGinty and Sterman, 1968; Szymusiak and McGinty, 1986; John et al., 1994, 1998; Sherin et al., 1996; John and Kumar, 1998; Khubchandani et al., 2005). Clinical evidence and experimentations over the last 80 years have led to the prevailing hypothesis that BF has SWS promoting or hypnogenic structures. More recently, sleep active neurons have been found to be concentrated in the vlPOA and mnPO (Gong et al., 2000; Lu et al., 2000). The importance of these cell groups is evident from c-fos expression during sleep state (Sherin et al., 1996).
To study the neural mechanism involved in the regulation of sleep, temperature and their interrelation we depend on the information obtained from lower animals. In cats, sleep was maximal at thermoneutral zone (TNZ) and that it decreases above and below TNZ (Parmeggiani et al., 1969). Subsequently several reports showed that the ambient temperature (T) produces complex changes in both NREM/SWS and REM sleep. The changes in sleep-wakefulness were studied in rats when they were exposed to different ambient temperature of 18, 24, and 30° C. (Thomas and Kumar, 2000). There was an increase in REM sleep and SWS, and a decrease in wakefulness at higher ambient temperature of 30° C. Even chronic exposure to 30° C. produced persistent increase in REM sleep (Mahapatra et al., 2005). According to one report on rats, NREM sleep and the metabolic rate were not affected much in between 23 and 31° C. However, the amount of REM sleep was at its peak at 29° C., and a marked decrease occurred at 33° C. (Szymusiak and Satinoff, 1981). Exposure of rats to gradual increase in ambient temperature from 18 to 30° C. produces a linear increase in the percentage of REM sleep (Szymusiak and Satinoff, 1984; Thomas and Kumar, 2000; Kumar et al., 2009). The increase in the amount of sleep may be considered as an adaptation to thermal load aimed at energy conservation (Obal et al., 1983). When human subjects were exposed to a range of ambient temperature, total sleep time (TST), NREM, and REM sleep were maximal at 29° C. (Haskell et al., 1981). But when they were exposed to T of 35° C., there was fragmented sleep with decrease in TST and increase in wakefulness, without any change in REM or delta sleep (Libert et al., 1988). Sleep is reduced when the T is lowered (Parmeggiani and Rabini, 1970; Schmidek et al., 1972; Szymusiak and Satinoff, 1984; Alfoldi et al., 1990; Rosenthal and Vogel, 1991; Ray et al., 2004). The TST, SWS, and REM sleep are decreased in rats when they are exposed to T of 18±1° C. for a few hours (Thomas and Kumar, 2000; Mahapatra et al., 2005). It was suggested that the central nervous system calls for an increase in the amount of arousal, at the expense of the sleep stages, especially REM sleep, in order to maintain the body temperature (T) when the T is low (Parmeggiani and Rabini, 1970; Alfoldi et al., 1990). An increase in arousal in cold T is necessary for the production of more heat (Schmidek et al., 1972; Parmeggiani et al., 1975).
As sleep is said to be influenced by T and the REM sleep is said to vary within the TNZ, it is important to address the question of TNZ for small animals. The most widely used method to study TNZ, i.e., minimum metabolic rate, has found the TNZ to be between 18 and 28° C. (Poole and Stephenson, 1977). Many others have described a range of 28-34° C. (Herrington, 1940; Clarkson et al., 1972; Gordon, 1987). According to another definition, the TNZ is “the range of T at which temperature regulation is achieved only by control of sensible heat loss.” Based on this the TNZ for Wistar rats have been reported to be between 29.5 and 30.5° C. (Romanovsky et al., 2002). Thus the suggested TNZ from all these studies vary from 18 to 34° C. Such contradictions described above emphasize that the TNZ for a given species, as determined by using a particular technique, is of little help in selecting the T for another study using a different variable. Therefore, before determining the responses to T on sleep, it makes sense to determine the TNZ of the animal using the behavioral criteria. Three different sets of temperatures (first set: 18, 24, and 27° C.; second set: 24, 27, and 30° C.; and third set: 27, 30, and 33° C.) were employed to study the thermal preference while looking into the influence of T on sleep architecture. It was found that the rats preferred to stay at 27° C., while the maximum sleep was obtained at 29-30° C. (Ray et al., 2004, 2005; Kumar et al., 2009, 2012). Sleep-wakefulness recordings during the day time in the nocturnal rats showed that the sleep followed a bell-shaped distribution, with a maximum during 11:00-15:00 hours (FIG. 2). The T , on the other hand, showed a reversed bell-shaped curve. The trough of T curve could be attributed to diurnal influence and sleep-related change (Obal et al., 1985; Alfoldi et al., 1990; Baker et al., 2005). The T trough disappeared at 30° C., though maximal REM sleep was recorded at the T of 30° C. The increased sleep at around the T of 30° C. may be a response to thermal load aimed at energy conservation (Obal et al., 1983). It was seen that the increase in thermal load at 30° C. attenuated the diurnal lowering of T. The ability to oppose diurnal shift in the T resides in the POA, as the lesion of this area produced higher diurnal change in the T in golden hamsters (Osborne and Refinetti, 1995). The POA could be involved in fine-tuning the body temperature to regulate sleep as per the requirement (Thomas and Kumar, 2002; Kumar, 2005). Though the maximum sleep was recorded at 30° C., the thermoregulatory diurnal oscillation was least disturbed only at 27° C. T.
These studies in rats suggest that sleep can be modulated by subtle changes in ambient temperature and raise the possibility that even minor changes in ambient temperature may influence sleep in significant manners.
Stimulation of central thermoreceptors by circulating blood temperature is likely to be an important source of impulses driving sleep inducing structures of BF (Moruzzi, 1972). Body and brain temperatures of rats are increased by more than 1° C. when the ambient temperature is increased from 21 to 29° C. (Alfoldi et al., 1990). This increase in body and brain temperatures may be responsible for the increase in SWS/NREM in animals and human subjects at warm T (Home and Staff, 1983; Home and Shackell, 1987; Shapiro et al., 1989; McGinty and Szymusiak, 1990; Morairty et al., 1993). This possibility is supported by the observation that local warming of the POA using chronically implanted water perfused thermode triggered SWS or EEG slow wave activity in rats, rabbits, and cats (McGinty and Szymusiak, 2003). Delta activity is also increased during this sustained SWS. Sustained increase in delta activity supports a hypothesis that sleep drive is modulated by thermosensitive neurons of the POA. On the other hand, both SWS and REM sleep were suppressed by mild cooling of the POA. Warm sensitive neurons (WSN) and cold sensitive neurons (CSN) have been identified in the POA on the basis of in vivo and in vitro studies (Nakayama et al., 1961, 1963). These neurons are identified on the basis of responses to local warming or cooling. Most WSN are sleep active, whereas CSN are wake active. The activities of posterior hypothalamic neurons, dorsal raphe in the midbrain, lateral hypothalamic orexinergic neurons, and BF cholinergic neurons are inhibited by the POA warming (Krilowicz et al., 1994; Alam et al., 1995a; Guzman-Marin et al., 2000; Methipara et al., 2003). These findings suggest the possibility that the WSN of the POA do have an inhibitory action on the arousal promoting neurons. Results from the POA warming studies indicate a homeostatic regulation by which sleep is promoted during mild rise of body temperature, which not only plays a thermoregulatory role but also serves as a protective mechanism to prevent the animal from venturing into a hostile thermal environment.
Based on the results of several studies it is concluded that both ambient and body temperatures profoundly influence sleep architecture (Home and Staff, 1983; Obal et al., 1983; Szymusiak and Satinoff, 1984; Home and Shackell, 1987; Shapiro et al., 1989; McGinty and Szymusiak, 1990; Morairty et al., 1993; Thomas and Kumar, 2000; Kumar et al., 2009). The thermoregulatory pathway which initiates heat and cold defense response is conveyed by skin thermoreceptors, en route dorsal horn, and parabrachial nuclei, to the POA (Nakamura, 2011). It is natural to assume that changes in sleep brought about by T is sensed and mediated by thermoreceptors. The roles of peripheral and central thermoreceptors have been investigated in order to get an insight into the role of afferent thermal inputs, from periphery and core, in the promotion of sleep. Capsaicin has been traditionally used for destruction of thermoreceptors and WSN. In an earlier report, sleep-wakefulness was studied in normal and capsaicin-treated rats when they were placed at T of 22 and 29° C. (Obal et al., 1983). There was an increase in sleep at the elevated temperature of 29° C., though REM sleep showed only a minor increase. The ambient temperature related increase in NREM sleep was not seen after destruction of peripheral and central warm receptors. There are different experimental models to explore the relative role of peripheral and central thermoreceptors in the T mediated sleep mechanism. In the first model, systemic administration of capsaicin in high doses destroys both peripheral and central warm receptors. In the second model, local application in the POA destroys WSN in this region only. In the third model, when neonatal rats are treated with capsaicin, their peripheral thermosensitivity is lost, while their central thermoregulatory neurons are preserved (Hajos et al., 1983). As mentioned earlier, when the rats were exposed to 27, 30, and 33° C., the rats had maximum sleep at 30° C., though they preferred to stay at 27° C. When both peripheral and central warm receptors, were destroyed in these rats (by systemic administration of capsaicin), the selective increase in REM sleep at 30° C. was not seen (Kumar et al., 2012). When peripheral warm receptors were selectively destroyed by neonatal treatment of capsaicin, the central warm receptors were able to mediate an increase in TST with increasing T, even in the absence of peripheral warm receptors (Gulia et al., 2005). This shows that the central WSN mediate the warm T related increase in SWS and REM sleep. When WSN of the POA were destroyed by local injection of capsaicin, the increase in REM sleep and SWS at 30° C. was not observed. SWS peak was brought down to 27° C., and REM sleep peak shifted to a higher temperature of 33° C., in these animals. The study clearly indicates that WSN of the POA mediate the increase in SWS, at temperatures higher than preferred T. The study shows that the neurons of the POA play a key role in regulating sleep as per homeostatic requirement (Kumar et al., 2011).
Much attention has been given to the physiological role of the POA, because of its ability to control thermoregulation and sleep. Many of the observations cited earlier support the hypothesis that sleep is modulated by thermosensitive neurons of the POA (Parmeggiani et al., 1975; Obal et al., 1983; McGinty and Szymusiak, 1990). Although this relationship has drawn considerable interest, it is still not known whether there is a “cause and effect” relationship or whether these changes are merely coincidental. Single unit studies clearly demonstrate that the POAH neurons, likely to be responsible for thermoregulation, are influenced by vigilance states (Alam et al., 1995a). The thermosensitivity of the POA neurons are reduced during SWS as compared to wakeful state (Parmeggiani et al., 1987). During SWS, a majority of WSN of POAH exhibit increased discharge rate. CSN exhibit less discharge during SWS and decreased thermosensitivity. The activation of these sleep-related WSN and inhibition of wake related CSN may play a role in the onset and regulation of SWS (Alam et al., 1995b). It could also be assumed that the POAH neurons which are responsible for sleep-wake modulations are thermosensitive (Szymusiak and McGinty, 1985; McGinty and Szymusiak, 2003). Most of the assertions that thermoreceptive elements control sleep regulation are based on results obtained from warming and cooling of the POAH neurons using thermodes. Warming of the POAH has been shown to suppress activity in the wake related magnocellular BF and posterior lateral hypothalamus of cats (Krilowicz et al., 1994; Alam et al., 1995a,b) and dorsal raphe and lateral hypothalamus of rats (Guzman-Marin et al., 2000; Methipara et al., 2003). These results suggest that WSN of the POAH may play a key role in the regulation of SWS sleep (Alam et al., 1995a,b; McGinty and Szymusiak, 2003). So, the modulation of sleep-wake state by POAH thermosensitive neurons must be viewed as a distinct possibility.
The influence of diurnal temperature rhythm on sleep is best studied in man. Both skin temperature and core body temperature show a day-night rhythm. In humans, the core temperature is relatively low during sleep at night and it is relatively high during waking period during day time. Skin temperature also exhibits a circadian rhythm, but its changes are reciprocal to that of the core body temperature rhythm (van Someren, 2006). The core body temperature and sleep propensity are negatively related, whereas skin temperature and sleep are positively related (Magnussen, 1939; Lack and Lushington, 1996). The degree of heat loss at the skin of the hands and feet is said to be the best physiologic predictor for a rapid sleep onset (Kräuchi et al., 1999, 2000). It was suggested that autonomous thermoregulatory changes in core body temperature and skin temperature could act as an input signal to modulate neuronal activity in sleep-regulating brain areas (van Someren, 2000). The activities of thermosensitive neurons in the POAH, are suggested to be modulated more strongly by changes in skin temperature, than by changes in core temperature (Boulant and Bignall, 1973). Manipulation of the skin temperature across the entire body within the TNZ can modulate sleepiness and sleep depth, even without activating thermoregulatory responses (Raymann et al., 2008). Even mild changes in skin temperature that occur during normal sleep can have an effect on sleep propensity not only in young adults but also in elderly subjects (Raymann and Van Someren, 2008). It remains unclear however if there are specific regions of the body that are most responsible for providing afferent thermal information to the POAH. The prior art teaches that the hands and feet may play a key role in the transmission of thermal information though it does not describe other body parts as significantly influencing these interactions.
Some studies support alterations in thermoregulation in insomnia patients. For example, one component of “hyperarousal” in insomnia that has been investigated as part of the pathopysiology of the disorder is an abnormal thermoregulation in insomnia patients. In healthy sleepers, there is a normal decline in core body temperature that occurs at sleep onset and continues throughout a night of sleep. Sewitch (1987) described abnormal elevations in core body temperature in insomnia patients and suggested that slow wave sleep deficiencies in insomnia is the result of a failure to down regulate temperature at the beginning of the night. Compared to controls, insomniacs are reported to have higher oral pre-sleep onset temperatures and, under ad lib sleep conditions, both higher rectal and oral temperatures over the sleep period. Finally, consistent with the inverse relationship reported between core body temperature and distal peripheral temperature, insomniacs are also reported to have lower finger temperatures in the minutes prior to sleep onset. By contrast, two studies reported no difference between insomniacs and controls in core body temperature and other correlates of arousal. Adam et al. observed no significant difference under ad lib sleep conditions in either post-sleep onset oral temperature or daytime adrenocortical activity in middle-aged to elderly insomniacs compared to controls. Similarly, Freedman and Sattler observed no difference in a variety of autonomic activity measures (e.g., EMG, heart rate, finger temperature) between young sleep onset insomniacs and controls during ad lib sleep. However, it is to be noted in both cases that the trends were in the expected direction. Despite evidence of an association between physiological arousal and insomnia it is noteworthy that the majority of studies have measured arousal under ad lib sleep conditions. This methodological limitation may account for some of the group differences reported between insomniacs and controls. For example, group differences in physical activity and posture rather than sleep quality may account for temperature differences. Similarly, core temperature may be elevated in insomniacs compared to controls during ad lib sleep conditions simply because temperature is elevated during wakefulness and by definition insomniacs spend a greater period of the night awake. In brief, it could be argued that elevated core body temperature is simply a result of sleep-wake state rather than an endogenous contributor to insomnia as the hyper-arousal model would suggest. More direct evidence that core body temperature is elevated in insomniacs has come from work by one group where they examined temperature under wakeful constant routine conditions. They found that aged insomniacs (primarily sleep maintenance insomniacs) compared to controls had higher core body temperatures prior to their habitual sleep onset time at home and that this persisted across the wakeful constant routine night until early morning when both groups converged and showed similar core temperature values across the remainder of the day. These findings suggest that aged sleep maintenance insomniacs are not chronically hyper-aroused across the 24-h period but are endogenously hyper-aroused at night. One other study of core temperature evaluated in a constant routine protocol failed to find differences between good sleepers and insomniacs during the day or at night. Whether this lack of difference arose from the use of a younger age group or smaller differences in objective sleep parameters between groups needs further investigation. The cumulative evidence provides some support for elevated core body temperatures in insomnia suggesting that thermoregulation may play an important role in the pathophysiology and perhaps treatment of insomnia.
The first study to investigate the skin temperatures of insomniacs attempting sleep was conducted in 1979 by Brown who found that insomniacs did show increases in toe skin temperature when attempting sleep, but that sometimes there was no observable change. Yet, when toe temperature increases were observed, they were more variable, and took twice as long to reach the same amount of temperature change compared to good sleepers. Freedman and Sattler found that compared to good sleepers insomniacs have significantly lower finger skin temperatures from lights out through to Stage 2 sleep onset. However, it appears that once sleep is achieved, differences in distal skin temperatures between insomniacs and good sleepers disappear, suggesting a critical period between lights out and sleep onset. It is worth noting that Freedman and Sattler found their insomniacs scored significantly higher on measures of general anxiety and worry compared to good sleepers, providing support for a link between anxiety, insomnia and lower distal skin temperature More recent attempts to investigate the notion that insomniacs have attenuated distal skin temperature increases when attempting sleep have found conflicting results. Other research confirmed that middle-aged insomniacs with sleep onset and maintenance difficulties reported both higher levels of general anxiety and sleep anticipatory anxiety in their home environments compared to good sleepers. Surprisingly though, the rapid increases in finger temperature of the insomniacs were found to be greater than those of good sleepers when they were falling asleep. However, it should be noted that in the laboratory the insomniacs fell asleep as quickly as the good sleepers and, in that sense, were not displaying their characteristic insomnia. The insomniacs did have significantly higher core body temperatures (by approximately 0.2-1 C) throughout the circadian rhythm thus supporting the chronic hyper-arousal theory for those suffering combined sleep onset and sleep maintenance insomnia. It would have been of interest for this study to have measured proximal skin temperature, as, along with core temperature, it would be likely to be higher in the insomniacs prior to the sleep attempt. If so, this would produce a lower distal/proximal skin temperature gradient associated with longer sleep latencies in normal sleepers. However, such a result would not negate the finding of a robust increase of distal skin temperature when insomniacs fell asleep. The chronically higher core temperature also suggests that there was a greater need for the insomniacs to lose core heat via the fingers and they appeared able to do so in the laboratory free of their previous insomnia symptoms. On the other hand, a recent study by van den Heuvel et al. suggested that insomniacs have less ability to vasodilate in distal skin. They found that younger sleep onset insomniacs had no greater finger temperature increase when challenged by a warm (45° C.) contralateral hand bath than a neutral bath (30-35° C.), whereas good sleepers showed a greater increase to the warm bath. However, because the baseline finger temperatures were not reported, it is not possible to rule out the possibility that the attenuated response in the insomnia group was due to a ceiling effect in their finger temperature. Regardless of whether insomniacs show attenuated vasodilation responses, it is still relevant, at least from a clinical perspective, to investigate whether skin warming would facilitate sleep onset. Raymann et al. have recently found that foot (distal) skin warming significantly facilitated shorter sleep onsets in young and elderly healthy sleepers, but not significantly in sleep disturbed elderly. Interestingly though, this elderly insomnia group showed the greatest slowing of reaction speed during proximal skin warming. Therefore, in good sleepers, and possibly in insomniac's skin warming seems conducive to sleepiness which is consistent with the earlier suggested link between warm sensitive and sleep inducing neurons in the hypothalamus. However, as in the two previous studies this one was also conducted in the laboratory during the day without insomnia evident according to their relatively short sleep latencies.
Notably, studies of skin temperature in insomnia patients have focused on distal skin temperatures in the feet and hands. Whether there are other more temperature sensitive regions of the body that can transmit temperature sensitive information to the POAH is not known.
So, while the relationships between skin temperature and sleep have been reported, the impact of selectively altering temperature at select skin regions aside from the feet and hands has not been clarified. Further, selective changes in these regions in the treatment of sleeplessness or insomnia have not been described.
Among body regions, the forehead has unique physiological and neuroanatomical properties that suggest it may play a prominent role in influencing the thermoregulatory hypothalamic modulation of sleep. The distribution of warm and cold spots has been shown to be highest over the face and forehead of all body parts (Lee and Tamura 1995; Rein 1925; Strughold and Porz 1931; Tamura and Lee 1995). Thermal sensation has been shown to be highest in the forehead of all body parts. In one study (Nadel et al 1973), thermal irradiation was applied to selected skin areas to determine whether particular areas demonstrate a greater thermal sensitivity than others in determination of a physiological thermoregulatory response. Modifications in thigh sweating rate were related to the change in temperature of the irradiated skin and the area of skin irradiated by computing a sensitivity coefficient for each skin area. Thermal sensitivity of the face, as measured by its effect on sweating rate change from the thigh, was found to be approximately three times that of the chest, abdomen and thigh. Lower legs were found to have about one-half the thermal sensitivity of the thigh. Other studies have reported that thermal sensitivity is highest in the face of all body areas (Crawshaw et al 1975; Stevens and Choo 1998; Stevens et al 1974). Further, the forehead comprising glabrous (non-hairy) skin has been shown to play a prominent role in the body response to thermoregulation given that the heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow (Hensley et al 2013).
These lines of evidence support the concept that application of a warming stimulus at the scalp on the forehead may be associated with improvements in sleep in insomnia patients via transmission of temperature sensitive information to the POAH. A medical device that alters skin temperature on the forehead, therefore, may be a very sensitive and non-invasive manner to regulate sleep in insomnia patients within a very narrow temperature range.